Formulation, Optimization and In-Vivo Characterization of Thermosensitive In-Situ Nasal Gel Loaded with Bacoside a for Treatment of Epilepsy.

The intranasal route has demonstrated superior systemic bioavailability due to its extensive surface area, the porous nature of the endothelial membrane, substantial blood flow, and circumvention of first-pass metabolism. In traditional medicinal practices, Bacopa monnieri, also known as Brahmi, is known for its benefits in enhancing cognitive functions and potential effects in epilepsy. This study aimed to develop and optimize a thermosensitive in-situ nasal gel for delivering Bacoside A, the principal active compound extracted from Bacopa monnieri. The formulation incorporated Poloxamer 407 as a thermogelling agent and HPMC K4M as the Mucoadhesive polymer. A 32-factorial design approach was employed for Optimization. Among the formulations. F7 exhibited the most efficient Ex-vivo permeation through the nasal mucosa, achieving 94.69 ± 2.54% permeation, and underwent a sol-gel transition at approximately 30.48 °C. The study's factorial design revealed that gelling temperature and mucoadhesive strength were critical factors influencing performance. The potential of in-situ nasal Gel (Optimized Batch-F7) for the treatment of epilepsy was demonstrated in an in-vivo investigation using a PTZ-induced convulsion model. This formulation decreased both the occurrence and intensity of seizures. The optimized formulation F7 showcases significant promise as an effective nasal delivery system for Bacoside A, offering enhanced bioavailability and potentially increased efficacy in epilepsy treatment.

The impact of Astragaloside IV on the inflammatory response and gut microbiota in cases of acute lung injury is examined through the utilization of the PI3K/AKT/mTOR pathway.

OBJECTIVES: Astragaloside IV (AS-IV) is a natural triterpenoid saponin compound with a variety of pharmacological effects, and several studies have clarified its anti-inflammatory effects, which may make it an effective alternative treatment against inflammation. In the study, we aimed to investigate whether AS-IV could attenuate the inflammatory response to acute lung injury and its mechanisms. METHODS: Different doses of AS-IV (20mg·kg-1, 40mg·kg-1, and 80mg·kg-1) were administered to the ALI rat model, followed by collection of serum and broncho alveolar lavage fluid (BALF) for examination of the inflammatory response, and HE staining of the lung and colon tissues, and interpretation of the potential molecular mechanisms by quantitative real-time PCR (qRT-PCR), Western blotting (WB). In addition, fecal samples from ALI rats were collected and analyzed by 16S rRNA sequencing. RESULTS: AS-IV decreased the levels of TNF-α, IL-6, and IL-1ß in serum and BALF of mice with Acute lung injury (ALI). Lung and colon histopathology confirmed that AS-IV alleviated inflammatory infiltration, tissue edema, and structural changes. qRT-PCR and WB showed that AS-IV mainly improved inflammation by inhibiting the expression of PI3K, AKT and mTOR mRNA, and improved the disorder of intestinal microflora by increasing the number of beneficial bacteria and reducing the number of harmful bacteria. CONCLUSION: AS-IV reduces the expression of inflammatory factors by inhibiting the PI3K/AKT/mTOR pathway and optimizes the composition of the gut microflora in AIL rats.

The effect of celastrol in combination with 5-fluorouracil on proliferation and apoptosis of gastric cancer cell lines.

Background: Despite the availability of chemotherapy drugs such as 5-fluorouracil (5-FU), the treatment of some cancers such as gastric cancer remains challenging due to drug resistance and side effects. This study aimed to investigate the effect of celastrol in combination with the chemotherapy drug 5-FU on proliferation and induction of apoptosis in human gastric cancer cell lines (AGS and EPG85-257). Materials and Methods: In this in vitro study, AGS and EPG85-257 cells were treated with different concentrations of celastrol, 5-FU, and their combination. Cell proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The synergistic effect of 5-FU and celastrol was studied using Compusyn software. The DNA content at different phases of the cell cycle and apoptosis rate was measured using flow cytometry. Results: Co-treatment with low concentrations (10% inhibitory concentration (IC10)) of celastrol and 5-FU significantly reduced IC50 (p < 0.05) so that 48 h after treatment, IC50 was calculated at 3.77 and 6.9 µM for celastrol, 20.7 and 11.6 µM for 5-FU, and 5.03 and 4.57 µM for their combination for AGS and EPG85-257 cells, respectively. The mean percentage of apoptosis for AGS cells treated with celastrol, 5-FU, and their combination was obtained 23.9, 41.2, and 61.9, and for EPG85-257 cells 5.65, 46.9, and 55.7, respectively. In addition, the 5-FU and celastrol-5-FU combination induced cell cycle arrest in the synthesis phase. Conclusions: Although celastrol could decrease the concentration of 5-fluorouracil that sufficed to suppress gastric cancer cells, additional studies are required to arrive at conclusive evidence on the anticancer effects of celastrol.

[Astragaloside IV reduces renal injury in mice with IgA nephropathy by inhibiting TIM-1 signaling pathway and increasing Th1/Th2 cell ratio].

Objective To investigate the effects of astragaloside IV(AS-IV) on the balance of T helper type 1 (Th1) and Th2 cells in mice with IgA nephropathy (IgAN) and its possible mechanism. Methods The IgAN model of BALB/c mice was established. Successfully modeled mice were randomly divided into four groups: model, AS-IV low dose, AS-IV medium dose and AS-IV high dose groups, with 10 mice in each group. Another 10 mice served as the control group. Mice in the low, medium and high dose groups were administered 12.5, 25 and 50 mg/kg AS-IV suspension (prepared in normal saline) by gavage, while the control and model groups were given an equivalent volume of normal saline. The 24-hour urinary protein (24 h UPr) content and urine red blood cell count were measured in each group. The levels of blood urea nitrogen (BUN), serum creatinine (Scr) and albumin (ALB) were determined. Serum interferon γ (IFN-γ), interleukin 4 (IL-4) and IL-10 levels were detected by ELISA. The ratio of Th1/Th2 cells in peripheral blood of mice was detected using flow cytometry. Histopathological changes in the kidney of mice were observed by HE staining. RT-PCR and Western blot were used to detect the mRNA and protein expressions of T cell immunoglobulin and mucin domain gene 1 (TIM-1), Toll-like receptor 4 (TLR4) in mouse kidney tissue. Results Compared with the model group, in weeks 12 and 15, the urine red blood cell count, 24 h UPr, BUN, Scr, levels of IL-4 and IL-10, the proportion of Th2 cells, as well as the mRNA and protein expression levels of TIM-1 and TLR4 were significantly decreased in the low, medium and high dose groups of AS-IV, and the levels of ALB, IFN-γ, the proportion of Th1 cells and Th1/Th2 cell ratio were increased, with the high-dose group showing the best effects. Conclusion AS-IV can inhibit TIM-1 signaling pathway, increase the Th1/Th2 cell ratio, inhibit the inflammatory reaction, and alleviate the renal injury in IgAN mice.

An anti-inflammatory active ingredients in Poriae cutis: Screening based on network pharmacology.

Hyperuricemia (HUA) is a disorder of uric acid metabolism, which can lead to the formation of gouty arthritis, kidney inflammation and other damages. Previous studies have found that the alcohol extract of Poria cutis can reduce the level of uric acid and protect against kidney injury. Based on network pharmacology, the core targets and main active components of P. cutis intervention in HUA were determined. Most of the potential active ingredients are triterpenoid acids such as tumulosic acid (TA) and eburicoic acid (EA), and the potential targets are TNF and IL-6, which are associated with inflammation. In vitro experiments have shown that TA can significantly inhibit the release of NO, TNF-α and IL-6 in inflammatory RAW264.7 cell culture medium and the expression of TNF-α and IL-6 in RAW264.7 cells. This study suggests that TA based on network pharmacological screening has obvious anti-inflammatory effect on inflammatory RAW264.7 cells and is a promising anti-inflammatory compound.

Ganopyrone A, a highly rearranged lanostane triterpenoid with antimalarial activity from artificially cultivated fruiting bodies of Ganoderma colossus.

Three previously undescribed highly modified lanostane triterpenoids, ganopyrone A, ganocolossusin I, and ganodermalactone Y, were isolated from the artificially cultivated fruiting bodies of the basidiomycete Ganoderma colossus TBRC-BCC 17711. Ganopyrone A possesses an unprecedented polycyclic carbon skeleton with an α-pyrone ring and C-18/C-23 bond. It showed antimalarial activity against Plasmodium falciparum K1 (multidrug-resistant strain) with an IC50 value of 7.8 µM (positive control: dihydroartemisinin, IC50 1.4 nM), while its cytotoxicity (Vero cells) was much weaker (IC50 103 µM).

Notoginseng leaf triterpenes promotes angiogenesis by activating the Nrf2 pathway and AMPK/SIRT1-mediated PGC-1/ERα axis in ischemic stroke.

Notoginseng leaf triterpenes (PNGL), derived from the dried stems and leaves of P. notoginseng, is a phytoestrogen that exerts many neuroprotective effects in vivo and in vitro of ischemic stroke. However, its impact on neurological restoration specifically in relation to angiogenesis following ischemic stroke remains unexplored. The aim of this study was to assess the effects of PNGL on angiogenesis subsequent to ischemic stroke. Male Sprague-Dawley rats were utilized in this study and were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). Post-ischemia, PNGL were administered through intraperitoneal (i.p.) injection. The high-performance liquid chromatography (HPLC) fingerprinting, triphenyltetrazolium chloride (TTC) staining, immunofluorescent staining, network pharmacology and western blot analyses were assessed to determine the therapeutical effect and molecular mechanisms of PNGL on cerebral ischemia/reperfusion injury. Our findings demonstrate that PNGL effectively reduced infarct volume, enhanced cerebral blood flow, and induced angiogenesis in rats subjected to MCAO/R. Notably, PNGL also facilitated neuronal proliferation and migration in HUMECs in vitro. The proangiogenic effects of PNGL were found to be linked to the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and the AMPK/SIRT1-mediated PGC-1/ERα axis, as well as the activation of neurological function. Our study provides evidence that PNGL hold promise as an active ingredient of inducing proangiogenic effects, potentially through the activation of the Nrf2 pathway and the AMPK/SIRT1-mediated PGC-1/ERα axis. These findings contribute to the understanding of novel mechanisms involved in the restoration of neurological function following PNGL treatment for ischemic stroke.

Six undescribed 23-norursane triterpenoids from the biotransformation of ilexgenin a by endophytic fungi and their vascular protective activity.

Biotransformation of ursane-type triterpenoid ilexgenin A by endophytic fungi Lasiodiplodia sp. MQD-4 and Pestalotiopsis sp. ZZ-1, isolated from Ilex pubescences and Callicarpa kwangtungensis respectively, was investigated for the first time. Six previously undescribed metabolites (1-6) with 23-norursane triterpenoids skeleton were isolated and their structures were unambiguously established by the analysis of spectroscopic data and single-crystal X-ray crystallographic experiments. Decarboxylation, oxidation, and hydroxylation reactions were observed on the triterpenoid skeleton. Especially, the decarboxylation of C-23 provided definite evidence to understand the biogenetic process of 23-norursane triterpenoids. Moreover, the qualitative analysis of the extract of I. pubescences showed metabolites 1, 3, 4, and 6 could be detected in the originated plant, indicating biotransformation by endophytic fungi is a practical strategy for the isolation of novel natural products. Finally, all isolates were evaluated for the protective activities against H2O2-induced HUVECs dysfunction in vitro. Compound 5 could improve the viability of endothelial cells and decrease the level of intracellular ROS.

The Biological Activity of Ganoderma lucidum on Neurodegenerative Diseases: The Interplay between Different Active Compounds and the Pathological Hallmarks.

Neurodegenerative diseases represent a cluster of conditions characterized by the progressive degeneration of the structure and function of the nervous system. Despite significant advancements in understanding these diseases, therapeutic options remain limited. The medicinal mushroom Ganoderma lucidum has been recognized for its comprehensive array of bioactive compounds with anti-inflammatory and antioxidative effects, which possess potential neuroprotective properties. This literature review collates and examines the existing research on the bioactivity of active compounds and extracts from Ganoderma lucidum in modulating the pathological hallmarks of neurodegenerative diseases. The structural information and preparation processes of specific components, such as individual ganoderic acids and unique fractions of polysaccharides, are presented in detail to facilitate structure-activity relationship research and scale up the investigation of in vivo pharmacology. The mechanisms of these components against neurodegenerative diseases are discussed on multiple levels and elaborately categorized in different patterns. It is clearly presented from the patterns that most polysaccharides of Ganoderma lucidum possess neurotrophic effects, while ganoderic acids preferentially target specific pathogenic proteins as well as regulating autophagy. Further clinical trials are necessary to assess the translational potential of these components in the development of novel multi-target drugs for neurodegenerative diseases.

PTEN status determines therapeutic vulnerability to celastrol in cholangiocarcinoma.

BACKGROUND: A balanced protein homeostasis network helps cholangiocarcinoma (CCA) maintain their oncogenic growth, and disrupting proteostasis therapeutically will induce proteotoxic stress. Phosphatase and tensin homolog (PTEN) have been reported to be involved in proteostasis, and PTEN-associated pathways are commonly altered in CCA. Celastrol, a triterpene from plants, exhibits cytotoxic effects in various types of cancer. However, the underlying mechanisms remain unclear. PURPOSE: We investigated the therapeutic effect of celastrol in CCA and identified the molecular characteristics of tumors that were sensitive to celastrol. The target of celastrol was explored. We then evaluated the candidate combination therapeutic strategy to increase the effectiveness of celastrol in celastrol-insensitive CCA tumors. METHODS: Various CCA cells were categorized as either celastrol-sensitive or celastrol-insensitive based on their response to celastrol. The molecular characteristics of cells from different groups were determined by RNA-seq. PTEN status and its role in proteasome activity in CCA cells were investigated. The CMAP analysis, molecular docking, and functional assay were performed to explore the effect of celastrol on proteasome activities. The correlation between PTEN status and clinical outcomes, as well as proteasomal activity, were measured in CCA patients. The synergistic therapeutic effect of autophagy inhibitors on celastrol-insensitive CCA cells were measured. RESULTS: Diverse responses to celastrol were observed in CCA cells. PTEN expression varied among different CCA cells, and its status could impact cell sensitivity to celastrol: PTENhigh tumor cells were resistant to celastrol, while PTENlow cells were more sensitive. Celastrol induced proteasomal dysregulation in CCA cells by directly targeting PSMB5. Cells with low PTEN status transcriptionally promoted proteasome subunit expression in an AKT-dependent manner, making these cells more reliant on proteasomal activities to maintain proteostasis. This caused the PTENlow CCA cells sensitive to celastrol. A negative correlation was found between PTEN levels and the proteasome signature in CCA patients. Moreover, celastrol treatment could induce autophagy in PTENhigh CCA cells. Disrupting the autophagic pathway in PTENhigh CCA cells enhanced the cytotoxic effect of celastrol. CONCLUSION: PTEN status in CCA cells determines their sensitivity to celastrol, and autophagy inhibitors could enhance the anti-tumor effect in PTENhigh CCA.

[Pristimerin enhances cisplatin-induced apoptosis in nasopharyngeal carcinoma cells via ROS-mediated deactivation of the PI3K/AKT signaling pathway].

OBJECTIVE: To explore the effect of pristimerin combined with cisplatin on proliferation and apoptosis of nasopharyngeal carcinoma cells. METHODS: CCK-8 assay was used to examine the survival rate of HNE-1 and CNE-2Z cells following treatment for 24 h with different concentrations of pristimerin, cisplatin or their combination. The changes in colony formation ability, apoptosis, and intracellular reactive oxygen species (ROS) levels of the treated cells were analyzed using colony formation assay and flow cytometry. Western blotting was performed to detect the changes in protein expressions in the cells. The effects of pre-treatment with NAC on proliferation, apoptosis, and PI3K/AKT signaling pathway were observed in pristimerin- and/or cisplatin-treated cells. RESULTS: Both pristimerin and cisplatin significantly lowered the survival rate of HNE-1 and CNE-2Z cells (P < 0.05). Compared with pristimerin or cisplatin alone, their combination more strongly inhibited survival and colony formation ability of the cells, increased cell apoptosis rate and intracellular ROS levels, upregulated the protein expressions of Bax, cleaved caspase-3, and cleaved PARP, and downregulated the protein expressions of Bcl-2, Mcl-1, PARP and p-PI3K and p-AKT (P < 0.05). NAC pretreatment significantly attenuated proliferation inhibition and apoptosis-promoting effects of pristimerin combined with cisplatin, and partially restored the downregulated protein expressions of p-PI3K and p-AKT in HNE-1 and CNE-2Z cells with the combined treatment (P < 0.05). CONCLUSION: Pristimerin can enhance cisplatin-induced proliferation inhibition and apoptosis in nasopharyngeal carcinoma cells, the mechanism of which may involve ROS-mediated deactivation of the PI3K/AKT signaling pathway.

Omaveloxolone ameliorates glucocorticoid-induced osteonecrosis of the femoral head by promoting osteogenesis and angiogenesis.

Steroid (glucocorticoid)-induced necrosis of the femoral head (SONFH) represents a prevalent, progressive, and challenging bone and joint disease characterized by diminished osteogenesis and angiogenesis. Omaveloxolone (OMA), a semi-synthetic oleanocarpane triterpenoid with antioxidant, anti-inflammatory, and osteogenic properties, emerges as a potential therapeutic agent for SONFH. This study investigates the therapeutic impact of OMA on SONFH and elucidates its underlying mechanism. The in vitro environment of SONFH cells was simulated by inducing human bone marrow mesenchymal stem cells (hBMSCs) and human umbilical vein endothelial cells (HUVECs) using dexamethasone (DEX).Various assays, including CCK-8, alizarin red staining, Western blot, qPCR, immunofluorescence, flow cytometry, and TUNNEL, were employed to assess cell viability, STING/NF-κB signaling pathway-related proteins, hBMSCs osteogenesis, HUVECs migration, angiogenesis, and apoptosis. The results demonstrate that OMA promotes DEX-induced osteogenesis, HUVECs migration, angiogenesis, and anti-apoptosis in hBMSCs by inhibiting the STING/NF-κB signaling pathway. This experimental evidence underscores the potential of OMA in regulating DEX-induced osteogenesis, HUVECs migration, angiogenesis, and anti-apoptosis in hBMSCs through the STING/NF-κB pathway, thereby offering a promising avenue for improving the progression of SONFH.

Semisynthesis and antitumor activity of endertiin B and related triterpenoids from Ganoderma lucidum.

Ganoderma lucidum, a fungus used in traditional Chinese medicine, is known for its medicinal value attributed to its active components called Ganoderma triterpenoids (GTs). However, the limited isolation rate of these GTs has hindered their potential as promising drug candidates. Therefore, it is imperative to achieve large-scale preparation of GTs. In this study, four GTs were effectively synthesised from lanosterol. The antitumor activity of these GTs was evaluated in vivo. Endertiin B exhibited potent inhibitory activity against breast cancer cells (9.85 ± 0.91 µM and 12.12 ± 0.95 µM). Further investigations demonstrated that endertiin B significantly upregulated p21 and p27 and downregulated cyclinD1 expression, arresting the cell cycle at the G0/G1 phase and inducing apoptosis by decreasing BCL-2 and increasing BAX and BAK levels. Additionally, endertiin B was found to reduce the expression of proteins associated with the PI3K-AKT signaling pathway. To summarize, endertiin B effectively inhibited cell proliferation by blocking the cell cycle and inducing apoptosis through the PI3K-AKT pathway.

Celastrol reduces lung inflammation induced by multiwalled carbon nanotubes in mice via NF-κb-signaling pathway.

Multiwalled carbon nanotubes (MWCNTs) have numerous applications in the field of carbon nanomaterials. However, the associated toxicity concerns have increased significantly because of their widespread use. The inhalation of MWCNTs can lead to nanoparticle deposition in the lung tissue, causing inflammation and health risks. In this study, celastrol, a natural plant medicine with potent anti-inflammatory properties, effectively reduced the number of inflammatory cells, including white blood cells, neutrophils, and lymphocytes, and levels of inflammatory cytokines, such as IL-1ß, IL-6, and TNF-α, in mice lungs exposed to MWCNTs. Moreover, celastrol inhibited the activation of the NF-κB-signaling pathway. This study confirmed these findings by demonstrating comparable reductions in inflammation upon exposure to MWCNTs in mice with the deletion of NF-κB (P50-/-). These results indicate the utility of celastrol as a promising pharmacological agent for preventing MWCNT-induced lung tissue inflammation.

Metabolomics combined with network pharmacology reveals a role for astragaloside IV in inhibiting enterovirus 71 replication via PI3K-AKT signaling.

BACKGROUND: Astragaloside IV (AST-IV), as an effective active ingredient of Astragalus membranaceus (Fisch.) Bunge. It has been found that AST-IV inhibits the replication of dengue virus, hepatitis B virus, adenovirus, and coxsackievirus B3. Enterovirus 71 (EV71) serves as the main pathogen in severe hand-foot-mouth disease (HFMD), but there are no specific drugs available. In this study, we focus on investigating whether AST-IV can inhibit EV71 replication and explore the potential underlying mechanisms. METHODS: The GES-1 or RD cells were infected with EV71, treated with AST-IV, or co-treated with both EV71 and AST-IV. The EV71 structural protein VP1 levels, the viral titers in the supernatant were measured using western blot and 50% tissue culture infective dose (TCID50), respectively. Network pharmacology was used to predict possible pathways and targets for AST-IV to inhibit EV71 replication. Additionally, ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) was used to investigate the potential targeted metabolites of AST-IV. Associations between metabolites and apparent indicators were performed via Spearman's algorithm. RESULTS: This study illustrated that AST-IV effectively inhibited EV71 replication. Network pharmacology suggested that AST-IV inhibits EV71 replication by targeting PI3K-AKT. Metabolomics results showed that AST-IV achieved these effects by elevating the levels of hypoxanthine, 2-ketobutyric acid, adenine, nicotinic acid mononucleotide, prostaglandin H2, 6-hydroxy-1 H-indole-3- acetamide, oxypurinol, while reducing the levels of PC (14:0/15:0). Furthermore, AST-IV also mitigated EV71-induced oxidative stress by reducing the levels of MDA, ROS, while increasing the activity of T-AOC, CAT, GSH-Px. The inhibition of EV71 replication was also observed when using the ROS inhibitor N-Acetylcysteine (NAC). Additionally, AST-IV exhibited the ability to activate the PI3K-AKT signaling pathway and suppress EV71-induced apoptosis. CONCLUSION: This study suggests that AST-IV may activate the cAMP and the antioxidant stress response by targeting eight key metabolites, including hypoxanthine, 2-ketobutyric acid, adenine, nicotinic acid mononucleotide, prostaglandin H2, 6-Hydroxy-1 H-indole-3-acetamide, oxypurinol and PC (14:0/15:0). This activation can further stimulate the PI3K-AKT signaling to inhibit EV71-induced apoptosis and EV71 replication.

Cornus officinalis Extract Enriched with Ursolic Acid Ameliorates UVB-Induced Photoaging in Caenorhabditis elegans.

Ultraviolet B (UVB) exposure can contribute to photoaging of skin. Cornus officinalis is rich in ursolic acid (UA), which is beneficial to the prevention of photoaging. Because UA is hardly soluble in water, the Cornus officinalis extract (COE) was obtained using water as the antisolvent to separate the components containing UA from the crude extract of Cornus officinalis. The effect of COE on UVB damage was assessed using Caenorhabditis elegans. The results showed that COE could increase the lifespan and enhance the antioxidant enzyme activity of C. elegans exposed to UVB while decreasing the reactive oxygen species (ROS) level. At the same time, COE upregulated the expression of antioxidant-related genes and promoted the migration of SKN-1 to the nucleus. Moreover, COE inhibited the expression of the skn-1 downstream gene and the extension of the lifespan in skn-1 mutants exposed to UVB, indicating that SKN-1 was required for COE to function. Our findings indicate that COE mainly ameliorates the oxidative stress caused by UVB in C. elegans via the SKN-1/Nrf2 pathway.

Structure-Activity Relationship of Oleanane-Type Pentacyclic Triterpenoids on Nuclear Factor κB Activation and Intracellular Trafficking and N-Linked Glycosylation of Intercellular Adhesion Molecule-1.

In our previous study, two oleanane-type pentacyclic triterpenoids (oleanolic acid and maslinic acid) were reported to affect the N-glycosylation and intracellular trafficking of intercellular adhesion molecule-1 (ICAM-1). The present study was aimed at investigating the structure-activity relationship of 13 oleanane-type natural triterpenoids with respect to the nuclear factor κB (NF-κB) signaling pathway and the expression, intracellular trafficking, and N-glycosylation of the ICAM-1 protein in human lung adenocarcinoma A549 cells. Hederagenin, echinocystic acid, erythrodiol, and maslinic acid, which all possess two hydroxyl groups, decreased the viability of A549 cells. Celastrol and pristimerin, both of which possess an α,ß-unsaturated carbonyl group, decreased cell viability but more strongly inhibited the interleukin-1α-induced NF-κB signaling pathway. Oleanolic acid, moronic acid, and glycyrrhetinic acid interfered with N-glycosylation without affecting the cell surface expression of the ICAM-1 protein. In contrast, α-boswellic acid and maslinic acid interfered with the N-glycosylation of the ICAM-1 protein, which resulted in the accumulation of high-mannose-type N-glycans. Among the oleanane-type triterpenoids tested, α-boswellic acid and maslinic acid uniquely interfered with the intracellular trafficking and N-glycosylation of glycoproteins.

Effect of betulin oil on hair growth in hypothyroidism- a long-term blinded pilot study.

BACKGROUND: One common problem in various patient groups is excessive hair loss on the head. One such group is people struggling with hypothyroidism. The market for preparations for hair growth and hair loss prevention includes betulin. PURPOSE: This pilot study investigated its effect on hair loss in hypothyroid patients. STUDY DESIGN: The study included a group of hypothyroid patients and a control group of people without hypothyroidism. Participants were randomly divided into a group taking placebo and betulin. METHODS: Results were investigated using photographic assessment of hair, trichoscopy and subjective evaluation of participants. CONCLUSION: The study did not conclusively prove that betulin would contribute to the inhibition of hair loss or regrowth.

Centella asiatica extract ameliorates deoxygenation-induced neurological dysfunction in zebrafish larvae.

Background: Oxygen deprivation (OD) is a critical condition that can lead to brain damage and even death. Current hypoxia management approaches are limited in effectiveness. Centella asiatica (CA), known for its neuroprotective properties, offers a potential alternative for OD treatment. Aims: This study aims to investigate the neuroprotective effects of CA on the expression of brain-derived neurotrophic factor (BDNF) and vesicular glutamate transporter 1 (VGLUT1) in zebrafish larvae under oxygen-deficient conditions. Methods: Zebrafish embryos were subjected to low oxygen levels (1.5 mg/l) 0-2 hours post-fertilization (hpf) until 3 days post-fertilization (dpf), simulating the early stages of OD. Subsequent treatment involved varying concentrations of CA (1.25-5 µg/ml) up to 9 days post-fertilization. The expression levels of BDNF and VGLUT1 were measured using PCR methods. Statistical analysis was conducted using a two-way analysis of variance to evaluate the impact of CA on the expression of BDNF and VGLUT1 in zebrafish larvae aged 3 and 9 dpf in oxygen-deprived conditions. Results: CA significantly influenced the expression of BDNF and VGLUT1 under OD (p < 0.001). An increase in BDNF expression (p < 0.001) and a decrease in VGLUT1 (p < 0.01) were observed in zebrafish larvae experiencing OD and treated with CA. There was no significant difference in BDNF and VGLUT1 expression across age variations in zebrafish larvae at 3 dpf and 9 dpf in the treatment groups (p > 0.05). CA concentration of 2.5 µg/ml effectively enhanced BDNF and reduced VGLUT1 in 3-9 dpf zebrafish larvae. Conclusion: CA demonstrates potential as a neuroprotective agent, modulating increased BDNF expression and reduced VGLUT1 under OD conditions. These findings lay a foundation for further research in developing therapies for oxygen deficiency.